Women who have small (≤ 1 cm), node-negative breast tumors “have an excellent prognosis without chemotherapy,” concluded the authors of a prospective cohort study involving 4,113 women with T1a,b, N0, M0 breast cancer. “Size and tumor subtype may identify patients in whom the rate of recurrence justifies consideration of chemotherapy,” the authors added. “These patients represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.”

Patients were identified through the National Comprehensive Cancer Network database and treated between 2000 and 2009. Eight centers nationwide contributed data to the analysis.

“There were striking differences in chemotherapy use between tumor subtypes,” the researchers noted in the Journal of Clinical Oncology. “Chemotherapy was rarely administered in patients with [hormone receptor]-positive/HER2-negative tumors [8%], and their pattern of care was unchanged over the last decade.” In contrast, 52% of those with HER2-positive or [hormone receptor]-negative/HER2-negative breast cancers received chemotherapy. There was an increase in the use of chemotherapy with or without trastuzumab [Herceptin] among patients with HER2-positive disease and in patients with T1a [hormone receptor]-negative/HER2-negative tumors over the past decade.

Survival Outcomes

“Survival outcomes diverged by subtype and size, but the 5-year distant relapse–free survival did not exceed 10% in any subgroup,” the researchers reported. The 5-year distant relapse–free survival was 97% for patients with T1a tumors untreated with chemotherapy and 95% for patients with T1b tumors.

“Patients with [hormone receptor]-positive/HER2-negative disease had the best [distant relapse–free survival] estimates, and patients with [hormone receptor]-negative/HER2-negative tumors had the lowest,” the investigators noted. The 5-year distant relapse–free survival was 100% for treated patients with hormone receptor–negative/HER2-negative T1a tumors and 96% for T1b tumors.

“This observational, nonrandomized cohort study calls into question what type of treatment is justified and appropriate for these patients,” the authors wrote. “In making decisions regarding adjuvant chemotherapy, the potential absolute benefits of treatment must be weighed against the treatment-related risks.”

They added, “Although the risk of death during breast cancer adjuvant chemotherapy is less than 1%, it is not absent, and there is a non-negligible risk of hospitalization or need for urgent evaluation for serious adverse effects related to chemotherapy. Other serious and lasting adverse effects include cardiomyopathy, secondary leukemias, and neuropathy.”

For most patients with T1a,b, N0, M0 breast tumors, the absolute benefit of chemotherapy with or without trastuzumab is relatively small, and “potential toxicities should be a factor in treatment decisions, which ultimately should be driven by a well-informed patient,” the researchers noted. “In the long run, we need to develop better ways to identify patients at the highest risk of recurrence while simultaneously trying to minimize treatment-related toxicity.” ■